tbuckley/cabot-search huggingface dataset:
Deep learning with whole slides images to predict histological response to neoadjuvant chemotherapy in patients with resectable high grade soft-tissue sarcomas: A multicenter study.
Authors: Benjamin Adjadj, Kathryn Schutte, Charles Maussion, Myriam Jean-Denis, Marie Karanian, Jean Michel Coindre, Antoine Italiano
Journal: Journal of Clinical Oncology (2023)

11512 Background: Two recent randomized trials have confirmed the potential benefit of neoadjuvant anthracycline-based chemotherapy in patients with high-grade soft-tissue sarcomas (STS) (Issels et al 2018, Gronchi et al 2017). However, as for adjuvant chemotherapy, the main issue with neoadjuvant treatment of STS patients is the identification of predictive factors of response to chemotherapy that could avoid for a majority of patients ineffective and potentially toxic treatment with impaired quality of life. Histological response, defined as the percentage of stainable tumor cells on the surgical specimen, has been shown to be a reliable surrogate for metastasis-free survival and overall survival in bone but also in soft-tissue sarcomas (Crombe et al JCO Clin Inf 2021). Developing a tool to help medical oncologists predict the potential benefit of neoadjuvant chemotherapy prior to starting the treatment would be of great value for precision medicine in sarcomas. To address this need, we propose a deep learning-based approach to predict histological response to neoadjuvant chemotherapy patients from routine histological whole slide images sampled at diagnosis. Methods: A cohort of 220 patients with high grade limb and trunk wall STS enrolled in the NEOSARCOMICS study (NCT02789384, sponsor: Institut Bergonié, Bordeaux, France) was used to train a model to predict the binarized histological response from diagnostic biopsies. Responders are defined by a histological response inferior or equal to 10%. Digitized hematoxylin/eosin slides were preprocessed to segment the tissue and decompose the image into patches of smaller resolution. Features were extracted from each patch using a Vision Transformer pretrained in a self-supervised fashion on histology slides. A Multiple Instance Learning model was trained on the resulting features to compute a prediction at the patient level. The algorithm was trained and validated through a 5-fold, 5-repeat cross-validation scheme. Finally, external validation is performed on an unseen cohort from Centre Léon Bérard to assess the robustness of the model. Results: To predict histological response to neoadjuvant chemotherapy, a model using only diagnostic biopsies achieved an AUC of 0.69 (95% confidence interval, 0.60-0.76). External validation is ongoing and shows promising preliminary results with an AUC of 0.67 (95% confidence interval with bootstrapping, 0.45-0.89). Conclusions: This multi-center study demonstrates that deep-learning models can accurately predict the histological response to neoadjuvant chemotherapy from routine histological whole slide images sampled at diagnosis. This model could be used as a pre-screening tool to improve patient selection for neoadjuvant chemotherapy in STS.
Skin cancer screening and sun safety education program for high school students in southern California.
Authors: David James Savage, Riley Gilbertson
Journal: Journal of Clinical Oncology (2023)

e22505 Background: Decreasing unprotected exposure to ultraviolet (UV) radiation during childhood can significantly decrease the risk of developing skin cancer as an adult. School-based sun safety curricula have demonstrated efficacy in teaching young adults about the harms of prolonged, unprotected UV exposure and have been effective in increasing safety practices. This project provided a 50-min sun safety curriculum to high school students at a public high school in San Diego, CA just prior to the summer break in 2022. The curriculum addressed skin cancer risk factors, skin protection methods, the benefits of limiting lifetime UV exposure, and methods for performing a skin self exam. The study objective was to assess sun safety knowledge before and after the class, and measure behavior changes three months thereafter when students returned from summer break. Methods: The sun safety classes were taught in groups of 40-60 students across six class periods in June 2022. Students were asked to complete an anonymous pre-participation online survey assessing their knowledge of common skin cancer types and skin cancer risk factors. Students were taught the curriculum over 45 minutes with 5 minutes reserved for questions. Two follow-ups surveys were conducted with the students, one at the end of the class period and a second follow-up three months later. Follow-up surveys assessed retention of knowledge and changes in sun safety behavior. Students had the option of providing a cell phone number so they could be contacted to participate in the second follow-up survey. Results: The curriculum was taught to nine classes of approximately 300 students in a single day across six class periods. A total of 206 students completed the pre-participation survey. At the first follow-up, 95.1% of students completed the post-participation survey and students showed significant improvement in knowledge of common skin cancer types (12.6% pre-participation to 68.9% post-participation), skin cancer risk factors (11.2% pre-participation to 16.8% post-participation), and skin cancer prevention methods (22.8% pre-participation to 45.9% post-participation). For the second follow-up, 128 students provided contact information and the survey had a response rate of 71.5%. After 3 months, students demonstrated retention of knowledge of skin cancer types and risk factors. A majority (87.2%) of students indicated that their use of sunscreen had increased and 57.4% indicated that their use of sun protective barriers had increased over the summer because of this course. Conclusions: This pilot course demonstrates that targeted sun safety education for teenagers before summer break can significantly increase sun safety awareness, adoption of protective behaviors, and knowledge about skin cancer. Such an intervention can promote skin cancer awareness at a young age where behavior changes can decrease lifetime risk of skin cancer.
Global impact of a video education platform on oncology education amongst healthcare professionals.
Authors: Yan Leyfman, Muskan Joshi, Shubhadarshini Pawar, Gayathri P. Menon, Maduri Balasubramanian, Ahmed Azeez, William B. Wilkerson, Shreevikaa Kannan, Sean Jackewicz, Emad B Zahid, Alexandra Van de Kieft, Harshal Chorya, Soumiya Nadar, Harashita Vallabhaneni, Pallavi Pai, Helena S Coloma, Steven Wilson, Chandler H. Park
Journal: Journal of Clinical Oncology (2023)

e23005 Background: Lower socioeconomic (SE) regions are often plagued extensively by healthcare outcome disparities. In searching for the root of this injustice, lack of access to the latest medical information has frequently been cited as a major contributor to these inequities. To address this, MedNews Week (MNW), a free, virtual education platform was developed to provide global health education through weekly oncology programming. The leading show, Keynote Conference, features live virtual presentations from oncology’s premier global leaders discussing the latest developments in the field. The aim of this study was to assess the global reach and impact of this platform for healthcare professionals (HCP). Methods: From September 2022 to January 2023, 37 MNW lectures on solid tumors and heme malignancies were showcased on VuMedi—a video platform providing free education content to HCP. Data collected from VuMedi included location, total page/video views, impressions, tumor subtype views and impressions, and occupation demographics. This information was analyzed to evaluate and assess the global reach of MNW on the VuMedi platform. Results: During this 5-month period, MNW experienced steady linear growth generating 5,643,257 page/video views with global viewership from 22 countries, including US, England, Canada, Brazil, and India (Table). Significant viewership was also observed from lower SE countries including Nigeria, Sudan, Georgia, and Bangladesh. Viewers were largely surgeons compared to Allied HCP (11:2). Higher viewership was observed for solid tumor presentations [706 (0.012%) page views and 9717 (7%) impressions] compared to heme malignancies [689 (0.001%) page views and 1688 (1.22%) impressions]. Within solid tumors, GI oncology keynotes were most viewed— generating 3755 (0.06%) page views and 28067 (20%) impressions, and the highest number of registrations recorded for this category. Conclusions: MNW continued growth in viewership and global reach amongst HCPs and demonstrates its emergence as a viable outlet to contribute to global oncology education, especially in lower SE areas. While previous studies have identified internet access and cost as barriers to high-quality medical information, MNW has experienced steady growth and reachability especially within these limited areas. The platform’s ability to showcase global leaders to HCP offers a practical approach to combat educational inequity and positively impact oncology education globally. [Table: see text]
Does community size impact survival with breast cancer? Data from a large population-based cohort in British Columbia.
Authors: Emily Beatrice Jackson, Lovedeep Gondara, Caroline H. Speers, Rekha M. Diocee, Alan Nichol, Caroline A. Lohrisch, Stephen Chia
Journal: Journal of Clinical Oncology (2023)

e18618 Background: Patients with breast cancer residing in rural settings have a unique set of challenges in accessing cancer care. How rural residence impacts disease-related outcomes is not fully understood. This study is a descriptive and quantitative analysis of geographically determined differences in patient presentations, treatment choices and outcomes for individuals diagnosed with breast cancer in rural and urban communities in British Columbia. Methods: Using BC Cancer’s Breast Cancer Outcomes Unit database, we identified all patients referred with newly diagnosed invasive breast cancer at any stage between 2005-2018. Using postal code, we then categorized patients as residing in either an urban (population ≥ 100,000) or rural setting ( &lt; 100,000), using the Statistics Canada classification of community size. We analyzed baseline clinical-pathological features, patterns of initial treatment, and outcomes differences between urban and rural settings. We performed a univariable analysis examining differences in locoregional relapse, distant relapse and breast cancer-specific survival (BCSS) between urban and rural cohorts. We then performed a multivariable analysis accounting for age, grade, lymphovascular invasion (LVI), subtype, stage, initial treatment with chemotherapy, endocrine therapy (ET), radiotherapy (RT) and type of definitive surgery. Results: The median follow up was 9.7 years for 35,255 patients. 9244 patients in rural and 26011 in an urban setting. There were no clinically meaningful differences in age, LVI, grade, subtype and stage at diagnosis between the urban and rural cohorts. Patients residing in a rural setting were significantly more likely to be treated with mastectomy (43.4% vs. 39.1%), less likely to receive RT (61.4% vs. 67.7%) and less likely to receive ET (67.2% vs. 71.7%). However, there was no difference in use of chemotherapy or anti-HER2 therapies between cohorts. On univariable analysis, urban residency was associated with improved BCSS (86.5% [86.0-86.9%] vs. 85.3% [95% CI: 84.5-86.1%], p &lt; 0.001), and lower risk of distant relapse (12.1% [11.7-12.6%] vs. 13.4% [12.6-14.1%], p &lt; 0.001). There was no influence on locoregional relapse. On multivariable analysis, urban residency was associated with improved BCSS, with a hazard ratio (HR) of 0.92 [0.86-0.99, p = 0.03], and lower risk of distant relapse (HR = 0.91 [0.85-0.98, p = 0.01]), but no influence on locoregional relapse. Conclusions: Rural residency is a significant and independent risk factor for both distant relapse and mortality from breast cancer. It is also associated with less use of ET and RT. Understanding the factors that contribute to these disparities is necessary to close the gap between rural and urban breast cancer outcomes.
Nanoparticle albumin-bound (nab) paclitaxel in combination with nivolumab as treatment of recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC) that progressed on a PD-1 inhibitor: A single-arm, phase 2 trial.
Authors: Jared Cohen, Peter John Oppelt, Sarah Pennock, Jingxia Liu, Jessica C. Ley, Douglas Adkins
Journal: Journal of Clinical Oncology (2023)

6023 Background: Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, an endocytic nutrient-scavenging process driven by constitutive hyper-activation of the EGFR, RAS, PIK3CA and Syndecan1 signaling pathways that frequently occur in HNSCC. nab-paclitaxel is an active drug in HNSCC and has immunologic effects that can prime an immune response to PD-1 inhibitors, potentially reversing resistance to these agents. These effects include decreased TREGs, increased pro-inflammatory macrophages and differentiation of MDSC to dendritic cells, increased HLA class I expression and antigen presentation, and recruitment of CD8+ CTLs into tumor. Methods: In a single-arm phase 2 trial, patients with RM-HNSCC that progressed on a PD-1 inhibitor received 28-day cycles of nab-paclitaxel (125 mg/m 2 IV days 1, 8, and 15) and nivolumab (480 mg IV day 1). Treatment continued until discontinuation criteria were met. The primary endpoint was objective response, assessed with RECIST1.1 by an independent radiologist. The primary hypothesis was that this regimen would result in a higher objective response rate (ORR) than historically reported with standard chemotherapy or cetuximab in similar patients. A Simon optimal two-stage design tested the null hypothesis (H 0 : ORR≤30%) versus the alternative hypothesis (H 1 : ORR=50%) at the type I error rate of 5% and power 0.80. In the first stage, 15 patients were to be accrued. If ≥6 responses occurred, 31 additional patients were to be accrued. The null hypothesis will be rejected if ≥19 responses are observed in these 46 patients. We report the results of the primary endpoint for the first stage of the trial. Results: 15 evaluable patients enrolled into the first stage of the trial. Key tumor characteristics and prior treatment history included HPV status (positive: 8; negative: 7), PD-L1 status (CPS 1-19: 7; ≥20: 8), # of lines of prior systemic treatment for RM disease (1-2: 12; ≥3: 3), interval (months) from prior PD-1 inhibitor (&lt;6: 11; ≥6: 4), duration (months) on prior PD-1 inhibitor (median: 6, range: 1-16), and best response to prior PD-1 inhibitor (PR: 4; SD: 6; PD: 5). Tumor response to nab-paclitaxel and nivolumab occurred in 7 of 15 patients (ORR 47%). The best tumor response was PR (7), SD (5) and PD (3). Conclusions: Among patients with RM-HNSCC that progressed on a PD-1 inhibitor, the ORR with nab-paclitaxel and nivolumab was 47% during the first stage of the phase 2 trial. Enrollment to the second stage is ongoing. Clinical trial information: NCT04831320 .
Real-world treatment outcomes in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who were treated with first-line single-agent ibrutinib vs. chemoimmunotherapy.
Authors: Ruibin Wang, Zhijie Ding, Xiaoxiao Lu, Heena Mavani, Jinghua He, Zaina P. Qureshi, Javier Pinilla-Ibarz
Journal: Journal of Clinical Oncology (2023)

e19509 Background: Real-world evidence on Bruton Tyrosine Kinase Inhibitor treatment vs chemoimmunotherapy (CIT) for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) has been limited to certain practice settings; research using a large and more comprehensive data source is warranted. Methods: This retrospective cohort study evaluated treatment outcomes among patients with CLL/SLL treated with first-line (1L) ibrutinib (IBR) or CIT using the US claims data from the Komodo Health payer-complete dataset, derived from &gt;150 private insurers and &gt;140 million insured individuals from 2015 to 2022. This study included adult patients with CLL/SLL who initiated 1L single-agent IBR or CIT (defined as no prior CLL/SLL treatment for ≥12 months in the baseline period) on or after March 2016. Time to next treatment (TTNT) was defined as the time from initiation (index date) of 1L treatment to treatment add-on or switch to a next line of therapy ≥29 days post-index and was compared using Cox proportional hazards models. Cohorts were balanced on baseline characteristics using inverse probability of treatment weights. Results: A total of 3570 1L IBR- and 2391 CIT-treated patients were included, with the mean age 68 vs 64 years, 63% vs 66% male, and mean Quan-Charlson Comorbidity Index score 2.87 vs 3.05, respectively. Median follow-up was 26 vs 31 months, and 13% vs 26% of patients recorded a next treatment during the study period for IBR and CIT, respectively. At 1-, 3-, and 5-year post-index, the probabilities (95% confidence interval [CI]) of not initiating a new treatment were 92% (91%-93%), 83% (81%-84%) and 76% (73%-78%) vs 88% (87%-89%), 70% (68%-73%) and 56% (53%-60%) for the IBR and CIT cohorts, respectively. After controlling for baseline characteristics, 1L IBR patients were significantly less likely to initiate the next line of therapy during the study period (hazard ratio 0.61, 95% CI 0.54-0.69, p&lt;0.001). Conclusions: 1L single-agent IBR was associated with a significantly lower risk of advancing to next line of treatment compared to CIT in this large claims-based data set, reinforcing real-world effectiveness of 1L IBR for CLL in an insured US patient population. [Table: see text]
Clinical outcomes of core binding factor acute myeloid leukemia in the modern era.
Authors: Yiwei Hang, Ian Michael Bouligny, Graeme Murray, Tilak Patel, Michael Doyel, Josh Boron, Valerie Tran, Juhi Gor, Thuy Ho, Kyle Zacholski, Chad Michael Venn, Yanal Mufeed Alnimer, Nolan Wages, Steven Grant, Keri Renee Maher
Journal: Journal of Clinical Oncology (2023)

e19054 Background: Acute myeloid leukemia (AML) with alterations in core binding factor (CBF) has a favorable prognosis. The impact of complex cytogenetics or ELN 2022 adverse genetic risk markers — such as ASXL1, RUNX1, EZH2, SRSF2, (and the rest of the secondary-type mutations [STMs]) and TP53 — in CBF-AML is unclear. Additionally, treatment outcomes in CBF-AML using front-line novel approaches, such as a hypomethylating agent (HMA; decitabine or azacitidine) with venetoclax, are unknown. This study analyzed outcomes of CBF-AML with respect to higher-risk molecular and cytogenetic cohorts and treatment approaches. Methods: We identified 58 consecutive patients with CBF-AML treated at VCU Massey Cancer Center from January 1, 2013 to January 1, 2022. We used Fisher’s exact test for between-group comparisons. We analyzed survival by the Kaplan-Meier method and compared groups with the log-rank test. The date of death was used to calculate overall survival; patients were censored at the date of the last contact. Measurable residual disease (MRD) was assessed using PCR-based methods or multiparameter flow cytometry with a minimum sensitivity of 10 -3 . Results: We analyzed 58 patients with inv(16) or t(8;21) AML treated in the front-line setting. Seven of these patients had concomitant genetic or molecular abnormalities typically considered high risk, including complex cytogenetics or TP53 mut . Forty-nine (84.5%) patients received intensive chemotherapy (IC) with FLAG, CPX-351, or conventional 7+3 with or without gemtuzumab ozogamicin; nine patients (15.5%) received lower-intensity therapies with HMAs with or without venetoclax. No differences in overall survival were seen between the patients with CBF-AML with or without complex cytogenetics or TP53 mut (not reached for either cohort, median follow-up time of 6.1 y. and 5.0 y., respectively, p = 0.969). There was no difference in the rates of MRD negativity in CBF-AML with or without complex cytogenetics or TP53 mut ( p = 0.544). The presence of secondary-type mutations also did not appear to significantly impact survival in CBF-AML ( p = 0.654). There was no difference in the rates of MRD negativity in CBF-AML with STMs and those without STMs ( p = 0.500). Patients that were ineligible for IC and were treated with venetoclax + HMA or HMA monotherapy had significantly reduced composite complete remission rates (CRR; CR + CRi; 25% vs 91.3%, p = 0.007) and median overall survival (3.7 m. versus not reached, p = 0.038). Conclusions: Our data confirm the superior outcomes in induction candidates of CBF-AML treated with IC. The presence of complex cytogenetics, TP53 mut , or secondary-type mutations did not appear to influence the rates of MRD negativity or overall survival in CBF-AML.
Mobocertinib efficacy in patients with NSCLC and <i>EGFR</i> exon 20 insertion mutations (ex20ins) identified by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA).
Authors: Joel W. Neal, Ying Li, Ziji Yu, Robert J. Fram, Christopher Danes, Sylvie Vincent, Zofia Piotrowska
Journal: Journal of Clinical Oncology (2023)

9082 Background: EGFR ex20ins are distinct targetable driver mutations present in ~2% of all NSCLC. While most EGFR TKIs have limited effectiveness, mobocertinib is the first oral therapy approved for this unmet need. EGFR ex20ins are heterogeneous ( &gt; 60 variants), and PCR testing detects a limited number of variants, leading to undetected disease in ~50% of cases, whereas NGS can identify all such mutations. Testing plasma ctDNA is a noninvasive approach for detection of genomic variants, such as EGFR ex20ins. Methods: In the mobocertinib phase 1/2 study (NCT02716116), patients were enrolled based on EGFR ex20ins detected by various local tissue or liquid clinical trial assays (CTAs). Baseline plasma samples were collected and processed to extract cell-free DNA and were evaluated for EGFR ex20ins status using FoundationOne Liquid CDX (F1LCDX), an NGS-based plasma ctDNA test. Concordance between F1LCDX and the CTAs was demonstrated by testing patient samples from the phase 1/2 trial and paired tissue and plasma samples from commercially acquired and stage-matched patients with NSCLC (N = 305). Efficacy analyses by assay method were performed in EGFR ex20ins–positive platinum-pretreated patients (PPP; n = 114 [FDA approved population]; data cutoff: 1 Nov 2021) in the phase 1/2 trial. Results: Concordance between F1LCDX and CTAs was demonstrated with samples from the CTA-positive (n = 159) and CTA-negative populations (n = 87) tested by F1LCDX where tissue and plasma were assessable; the point estimate of positive percentage agreement (95% CI) was 68.6% (61.0–75.3), and the point estimate of negative percentage agreement was 100% (95.8–100). F1LCDX detected 34 individual EGFR ex20ins variant types. In the response evaluable population, patients who tested EGFR ex20ins positive by F1LCDX (n = 55) demonstrated confirmed ORR (34.5%) and disease control rate (74.5%), which was comparable to those observed among all PPP in the phase 1/2 trial (confirmed ORR: 28%; confirmed disease control rate: 78%). Conclusions: Mobocertinib has shown efficacy in PPP with EGFR ex20ins NSCLC. F1LCDX effectively identified patients with EGFR ex20ins who may benefit from mobocertinib, providing an additional noninvasive diagnostic option to guide treatment. Clinical trial information: NCT02716116 .